Lack of bioavailability of mebeverine even after pretreatment with pyridostigmine.
OBJECTIVE
After the oral administration of mebeverine to animal or human, measurable concentrations of the drug have never been found in the plasma. The ex vivo hydrolysis of mebeverine can be blocked by esterase inhibitors. In the present study, human volunteers were pretreated with pyridostigmine to attempt to improve the bioavailability of the parent drug.


METHODS
Following a single-blind, random design, 12 normal human volunteers received orally either placebo or 60 mg pyridostigmine, followed 2 h later by 405 mg mebeverine. Blood samples were drawn intermittently for 4 h and were spiked immediately with neostigmine in order to block ex vivo hydrolysis.


RESULTS
Even after pretreatment with pyridostigmine, the plasma samples failed to reveal detectable concentrations of mebeverine. Pyridostigmine pretreatment mediated a significantly higher peak concentration of veratric acid, the acid moiety resulting from hydrolysis of mebeverine.


CONCLUSIONS
As mebeverine seemingly undergoes complete presystemic hydrolysis, it seems unlikely that the effects of the drug could be mediated centrally. Furthermore, as it is unlikely that sufficient mebeverine traverses the intestine to exert a local effect on the colon (i.e., the time-course of veratric acid plasma levels does not support such a conclusion), the therapeutic effect of the drug, if any, has to be ascribed to an active metabolite. However, the hydrolysis products of mebeverine are not known to be pharmacologically active.
Sommers
D K
DK
Department of Pharmacology, Faculty of Medicine, Pretoria, South Africa.
Snyman
J R
JR
van Wyk
M
M
Eloff
J N
JN
D001682:Biological Availability; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D010276:Parasympatholytics / Q000493:pharmacokinetics*; D010627:Phenethylamines / Q000493:pharmacokinetics*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D016037:Single-Blind Method
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D010627:Phenethylamines; C005096:mebeverine; D011729:Pyridostigmine Bromide